A Study to Look at Tapentadol Oral Solution in Children a... | NCT02081391 | Trialant
NCT02081391
Sponsor
Grünenthal GmbH
Status
Completed
Last Update Posted
Jan 18, 2020Actual
Enrollment
216Actual
Phase
Phase 3
Conditions
Acute Pain
Interventions
Tapentadol oral solution 4 mg/mL
Tapentadol oral solution 20 mg/mL
Placebo
Countries
United States
Bulgaria
Croatia
Czechia
France
Germany
Hungary
Poland
Spain
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02081391
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
KF5503/65
Secondary IDs
ID
Type
Description
Link
2012-004359-35
EudraCT Number
Brief Title
A Study to Look at Tapentadol Oral Solution in Children and Adolescents in Pain
Official Title
An Evaluation of the Efficacy and Safety of Tapentadol Oral Solution in the Treatment of Post-operative Acute Pain Requiring Opioid Treatment in Pediatric Subjects Aged From Birth to Less Than 18 Years Old
Acronym
Not provided
Organization
Grünenthal GmbHINDUSTRY
Status Module
Record Verification Date
Jan 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 19, 2015Actual
Primary Completion Date
Mar 3, 2019Actual
Completion Date
Mar 14, 2019Actual
First Submitted Date
Mar 5, 2014
First Submission Date that Met QC Criteria
Mar 5, 2014
First Posted Date
Mar 7, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 9, 2019
Results First Submitted that Met QC Criteria
Jan 15, 2020
Results First Posted Date
Jan 18, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 15, 2020
Last Update Posted Date
Jan 18, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Grünenthal GmbHINDUSTRY
Collaborators
Name
Class
Depomed
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of the study was to evaluate the efficacy of tapentadol oral solution, based on the total amount of supplemental opioid analgesic used over 12 hours or 24 hours after initiation of investigational medicinal product (IMP) in children and adolescents who had undergone surgery that would produce moderate to severe pain during opioid treatment.
Detailed Description
The supplemental opioid medication reflecting the standard of care was available as patient- or nurse-controlled intravenous (i.v.) morphine or hydromorphone. This supplemental opioid analgesic medication (SOAM) was given to control pain, as needed, in both the treatment and placebo groups.
Children and adolescents 6 months and older were dosed with a dose regimen of 1.25 mg/kg body weight for the first 24 hours of treatment. 24 hours after the start of study medication (and based on clinical judgment), a dose reduction to 1.0 mg/kg was allowed.
Participants 30 days to less than 6 months old were dosed with a regimen of 0.5 mg/kg for the first 24 hours of treatment. The dose of IMP could be reduced after 24 hours to 0.3 mg/kg (if there was a reduced need for analgesia according to the investigator's judgment).
Participants aged from birth to less than 30 days old were dosed with a regimen of 0.1 mg/kg for the first 24 hours of treatment. The dose of the IMP could be reduced after 24 hours to 0.075 mg/kg (if there was a reduced need for analgesia according to the investigator's judgment).
The decision to maintain or alter the dose based on the effectiveness of the analgesia (pain killer) and the adverse event profile observed in each participant over the first 24-hour dosing period was made based on the investigator's judgment.
In exceptional cases, if a participant had unbearable pain despite using nurse-controlled analgesia (NCA) or patient-controlled analgesia (PCA), an additional bolus (defined as a clinician bolus) of morphine or hydromorphone could have been administered. The clinician bolus could have been given either using the NCA/PCA pump system or by an intravenous bolus injection. The opioid given as a clinician bolus or if the NCA/PCA intravenous line failed, had to be the same opioid used in the NCA/PCA pump system.
Dosing with IMP was stopped if:
A switch to exclusively oral opioid analgesic medication was indicated according to the local standard of care.
Opioid analgesic medication was no longer needed.
IMP had been administered for 72 hours.
Safety evaluations included assessment of adverse events, physical examination, vital signs, laboratory parameters, electrocardiogram, oxygen saturation, and, only for children older than 6 years of age, a scale to assess suicidal ideation (Columbia Suicide Severity Rating Scale [C-SSRS]). The maximum study duration for each participant was 42 days.
The evaluation of the safety and efficacy data was performed by age groups as aligned with European and United States agencies. Within the tapentadol treatment group, no analysis by tapentadol dose was conducted. Results for participants aged 2 years to <18 years were provided to the Pediatric Committee of the European Medicines Agency (EU PDCO) before recruitment of the children less than 6-month old required for the US Food and Drug Administration [FDA] analysis was completed. Participants from birth to <2 years old were analyzed separately for the US FDA only and not included in the analysis of the population aged from 2 years to <18 years.
Conditions Module
Conditions
Acute Pain
Keywords
Acute Pain
Post-operative
Tapentadol
Opioid Treatment
Pediatric Participants
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
216Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Tapentadol immediate-release (IR)
Experimental
In the first 24 hours, tapentadol oral solution at a dose of 1.25 mg/kg body weight was given every 4 hours (±15 min) to participants aged 6 months to less than 18 years (maximum individual dose of tapentadol was 100 mg). Participants from 30 days to less than 6 months were dosed with 0.5 mg/kg body weight every 4 hours. Participants from birth to less than 30 days of age were dosed with 0.1 mg/kg body weight every 4 hours.
After 24 hours and up to 72 hours, the dose could be reduced based on the investigator's judgment.
Drug: Tapentadol oral solution 4 mg/mL
Drug: Tapentadol oral solution 20 mg/mL
Placebo
Placebo Comparator
Matching placebo oral solution was administered every 4 hours (±15 min) up to 72 hours.
Other: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Tapentadol oral solution 4 mg/mL
Drug
Participants aged 6 months to less than 18 years old with a body weight below 20 kg received tapentadol oral solution 4 mg/mL by mouth every 4 hours for up to 72 hours.
Participants from birth to less than 6 months received tapentadol oral solution, diluted 4 fold.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
For the US FDA: The Total Amount of Supplemental Opioid Analgesic Medication Used Within the First 12 Hours After First Intake of Investigational Medicinal Product (IMP) [Tapentadol Oral Solution or Placebo]
The primary endpoint for the United States Food and Drug Administration (US FDA) (and secondary endpoint for the Pediatric Committee of the European Medicines Agency [EU PDCO]) was the total amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set (from 2 years to <18 years old) within 12 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Up to 12 hours
For the EU PDCO: The Total Amount of Supplemental Opioid Analgesic Medication Used Within the First 24 Hours After First Intake of IMP [Tapentadol Oral Solution or Placebo]
The primary endpoint for the EU PDCO (and secondary endpoint for the US FDA) was the total amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set (from 2 years to <18 years old) within 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Up to 24 hours
Secondary Outcomes
Measure
Description
Time Frame
Total Amount of Supplemental Opioid Analgesic Medication Received, Assessed in 12-hour Intervals From 24 Hours to 96 Hours After the First Dose of IMP
The total amount of supplemental opioid analgesic medication (SOAM) received was assessed in 12-hour intervals from 24 hours to 96 hours after the first dose of IMP for participants who were administered SOAM.
SOAM use was expressed in mg/kg of morphine i.v. equivalents.
Other Outcomes
Measure
Description
Time Frame
Mean Amount of Supplemental Opioid Analgesic Medication Use After First Intake of Investigational Medicinal Product in Children Aged From Birth to Less Than 2 Years
The mean amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set subset aged from birth to less than 2 years old was determined from 0 to 12 hours and from 0 to 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Informed consent, and if applicable assent, given according to local regulations.
Male or female participant aged from birth (at least 37 weeks gestational age) to less than 18 years.
A female participant must be pre-menarchal, or surgically incapable of childbearing, or sexually abstinent, or if a female participant is sexually active, then she must be practicing an effective method of birth control (e.g., prescription hormonal contraceptives, intra-uterine devices used according to the product's instruction, double-barrier methods) before trial entry and throughout the trial.
A female participant must have a negative pregnancy test if aged 12 years or older, or is post-menarchal, or is sexually active.
Participant has undergone surgery (other than brain surgery or gastrointestinal surgery expected to affect the absorption of tapentadol [in the investigator's judgment]) that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment for at least 24 hours after first dose of IMP. Participants must remain hospitalized until the End of Treatment Visit.
Participant has received post-operative morphine or hydromorphone by NCA/PCA, with or without a background infusion of the same opioid, according to standard of care prior to allocation/randomization to IMP and participant is expected to require this morphine or hydromorphone by NCA/PCA after starting IMP.
Participant is able to tolerate liquids at the time of allocation/randomization to IMP.
Exclusion Criteria:
Participant, parent or the legal representative is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, or family member of the employees or the investigator.
Participant has been previously exposed to tapentadol.
Participant has received an experimental drug or used an experimental medical device within 28 days before allocation/randomization to IMP, or within a period less than 10 times the drug's half-life, whichever is longer.
Participant has a history or current condition of any one of the following:
Non-febrile seizure disorder.
Epilepsy.
Serotonin syndrome.
Traumatic or hypoxic brain injury, brain contusion, stroke, transient ischemic attack, intracranial hematoma, post-traumatic amnesia, brain neoplasm, or episode(s) of unconsciousness of more than 24 hours.
Participant has a history or current condition of any one of the following:
Moderate to severe renal or hepatic impairment.
Abnormal pulmonary function or clinically relevant respiratory disease (e.g., acute or severe bronchial asthma, hypercapnia).
Participant has a concomitant disease or disorder (e.g., endocrine, metabolic, neurological, psychiatric, infection, febrile seizure, paralytic ileus) that in the opinion of the investigator may affect or compromise participant safety during the study participation.
Participant has history of suicidal ideation or behavior.
Participant is obese in the investigator's judgment. Obesity can be determined based on appropriate body mass index (BMI) charts or tables; e.g., a BMI above the 97th percentile for children based on the World Health Organization growth charts or the participant's weight is less than 2500 grams.
Participant has a clinically relevant history of hypersensitivity, allergy, or contraindication to the supplemental opioid analgesic medication or tapentadol, or the excipients, or naloxone.
Participant is not able to understand and comply with the protocol as appropriate for the age of the participant or participant is cognitively impaired in the investigator's judgment such that they cannot comply with the protocol
Participant has a history of alcohol and/or substance abuse in the investigator's judgment based on participant's history and physical examination.
Participant is taking prohibited concomitant medication.
Participant has received a long-acting opioid for the treatment of pain following surgery within 6 hours of allocation/randomization to IMP.
Participant has clinically relevant (in the investigator's judgment) abnormal values for clinical chemistry or hematology (local laboratory sample taken after surgery).
A participant aged 6 months to less than 18 years old is excluded if the:
Aspartate transaminase or alanine transaminase is greater 3-times upper limit of normal.
Total bilirubin is greater 2-times upper limit of normal (except if the cause is due to Gilbert's syndrome).
Glomerular filtration rate less than 60 mL/min.
A participant aged from birth to less than 6 months old is excluded if:
Aspartate transaminase or alanine transaminase is >3-times upper limit of normal.
There is pathological jaundice in the opinion of the investigator.
Glomerular filtration rate (calculated according to Schwartz et al. 1984) is:
<20 mL/min/1.73 m2 for participants <1 week post-partum.
<30 mL/min/1.73 m2 for participants 1 week to 8 weeks post-partum.
<50 mL/min/1.73 m2 for participants >8 weeks postpartum to <6 months old.
QT or corrected QT interval (QTc) interval >470 ms for children aged 6 years to less than 18 years old.
QT or QTc interval >460 ms for children aged from birth to less than 6 years old.
Peri- or post-operative analgesia supplied by a continuous regional technique (e.g., nerve block, wound infiltration catheter) or participant-controlled epidural analgesia that was terminated less than 6 hours before allocation/randomization to IMP.
Participant has post-operative clinically unstable systolic and diastolic blood pressure, heart rate, respiratory depression, or clinically unstable upper or lower airway conditions (in the investigator's judgment), or a saturation of peripheral oxygen (SpO2) <92% at the time of randomization (allocation/randomization to IMP).
Female participant is breast-feeding a child.
Participant requires continuous positive airway pressure or mechanical ventilation, at the time of allocation to IMP.
The mother of a newborn participant or the breastfeeding mother of a participant was administered a prohibited medication.
Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr. 1984 Jun;104(6):849-54. doi: 10.1016/s0022-3476(84)80479-5.
A total of 216 participants (or parents/caregivers) gave informed consent to participate in the trial, 180 of these participants were allocated to study drug (investigational medicinal product = IMP) and 175 participants received IMP (56 participants received placebo oral solution and 119 participants received tapentadol oral solution).
Recruitment Details
The trial started on 19 Feb 2015 with the enrollment of the first participant. Recruitment of participants aged 2 to <18 years old was completed on 05 Dec 2016 with the last participant out. Recruitment of the remaining participants aged from birth to <2 years old was completed on 14 Mar 2019.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Tapentadol (From 2 to <18 Years)
This arm includes all participants aged 2 years to less than 18 years who had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA or PCA and who received at least 1 dose of tapentadol oral solution.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours. 24-hour treatment completers were defined as those who did not discontinue treatment before 24 hours; trial completers completed 24 hours of treatment and attended the follow up visit.
Periods
Title
Milestones
Reasons Not Completed
12-hour Treatment
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Mar 24, 2017
Sep 11, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Austria
Puerto Rico
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Quadruple
Masking Description
The trial was double-blinded to prevent bias. The blind was broken for the participants aged 2 years to <18 years (Pediatric Committee of the European Medicines Agency [EU PDCO] set) before recruitment of the <6 month-old subjects for the United Sates Food and Drug Administration (US FDA) set (which comprised participants from birth to <18 years) was completed. Participants not belonging to the EU PDCO set (<2 years old) remained blinded (as independent randomization lists were used for participants aged <2 years old) and were unblinded only after the data base was locked for all participants from birth to <2 years old who were included in the US FDA <2 years population.
Participants aged from 6 months to less than 18 years with a body weight greater than or equal to 20 kg received tapentadol oral solution 20 mg/mL by mouth every 4 hours for up to 72 hours.
Tapentadol immediate-release (IR)
Placebo
Other
Matching placebo oral solution was administered by mouth every 4 hours up to 72 hours.
Placebo
Up to 96 hours
Palatability of IMP After First Dose Assessed Using Facial 5-point Hedonic Scale
Palatability of IMP after the first dose was assessed in participants aged 2 years to less than 18 years using 5-point hedonic scales in combination with verbal rating. A question "How does the medication taste" was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range where 5 = really good, 4 = good, 3 = a bit good/a bit bad, 2 = bad, and 1 = really bad. Higher scores represent good palatability. Responses were summarized. Missing values were not imputed.
Palatability data was not collected for participants <2 years old.
Up to 96 hours
Acceptability of IMP After First Dose Assessed Using Facial 5-point Hedonic Scale
Acceptability of IMP in participants aged 2 years to less than 18 years was assessed using 5-point hedonic scales in combination with verbal rating. A question "Swallowing the medication is..." was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range, with 5 = really easy, 4 = easy, 3 = a bit easy/a bit difficult, 2 = difficult, and 1 = really difficult. Higher scores represent better acceptability.
Responses were summarized. Missing values were not imputed. Acceptability data was not collected in participants <2 years old.
Up to 96 hours
Change From Baseline in the Face, Leg, Activity, Cry, and Consolability (FLACC) Total Score in Participants Aged Less Than 6 Years
The FLACC scale was used for children from birth to less than 6 years, or in older children who were not able to report their pain using the other scales. This tool includes 5 categories of pain behaviors: facial expression (F), leg movement (L), activity (A), cry (C), and consolability (C). Each of the 5 categories is scored 0, 1 or 2. The total score between 0 and 10 is the sum of the 5 individual categories. Higher scores represent worse condition.
The Pain intensity scores were obtained before and after first dose of IMP, and before each subsequent dose of IMP, whenever possible, up to end of treatment (96 hours).
Changes from baseline values were summarized descriptively for each time point.
Up to 96 hours
Change From Baseline Pain Intensity Using the Faces Pain Scale-Revised (FPS-R) in Participants Aged 6 to Less Than 12 Years
For children aged 6 years (if possible) to less than 12 years, pain intensity was assessed by the use of the Faces Pain Scale-Revised (FPS-R). The FPS-R is a validated self-reported 6-point scale (0, 2, 4, 6, 8, 10) with 0 representing no pain and 10 representing very much pain. Facial representations were used to indicate how much the pain hurts. Higher scores represent worse condition.
Pain intensity scores were obtained before and after first dose of IMP, and before each subsequent dose of IMP, whenever possible.
Changes from baseline pain values were summarized descriptively for each time point up to end of treatment (96 hours).
Up to 96 hours
Change From Baseline in the Visual Analog Scale (VAS) Pain Intensity Score in Participants Aged 12 to Less Than 18 Years
For children and adolescents aged 12 years to less than 18 years, pain intensity was assessed by the use of a Visual analog scale (VAS). The participant was asked to draw a single line to indicate the current level of pain intensity on a 100 mm long scale by marking a point on the line in response to: "My pain right now is". The mark was scored between "no pain" and "pain as bad as it could be". A value of 0 indicates "no pain". A value of 100 indicates "pain as bad as it could be". Pain intensity scores were obtained before and after first dose of IMP, and before each subsequent dose of IMP, whenever possible. Changes from baseline values were summarized descriptively for each time point.
Up to 96 hours
Clinical Global Impression of Change (CGIC)
The CGIC was assessed at the End of Treatment Visit (Day 4). The investigator rated the participant's global improvement and satisfaction with the treatment on a 7-point scale with 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worsening. Results were summarized descriptively.
Day 4
Patient Global Impression of Change (PGIC)
The PGIC was assessed at the End of Treatment Visit (Day 4). Participants rated their impression of overall status on a 7-point scale with 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worsening. If participants were not capable of completing the questionnaire, the parent/legal guardian could completed the questionnaire on behalf of the participant.
Results were summarized descriptively.
Day 4
Time to Receive First and Second Patient- or Nurse-controlled Analgesia After the First Dose of IMP
The time to first and time to second patient-controlled analgesia (PCA) or nurse-controlled analgesia (NCA) after the first dose of IMP were summarized descriptively using time-to-event methods and are displayed by relevant treatment groups. Participants who completed the End of Treatment Visit (scheduled for 96 hours after first IMP) before their first/second use of NCA/PCA or participants who terminated treatment before their first/second use of NCA/PCA were censored at the End of Treatment Visit.
Time-to-event variables are reported using Kaplan-Meier analyses. Therefore, values might remain missing if the survival function does not reach a respective threshold. This is indicated by not applicable (NA).
Up to 96 hours
Time From First Dose of IMP Until Treatment Discontinuation Due to Lack of Efficacy
The distributions of the time from the first dose of IMP to treatment discontinuation due to lack of efficacy were summarized descriptively using time-to-event methods.
Participants who reached the maximum duration of treatment (72 hours) were censored at 72 hours after first IMP intake. Participants who discontinued during the Treatment Period for reasons other than lack of efficacy were censored at the time of the decision to discontinue treatment.
Due to the low number of participants with events in the age group from 2 to <18 years, the median time and the corresponding confidence interval could not be calculated. The number of participants who discontinued early due to lack of efficacy is presented instead.
Up to 72 hours
Palatability of IMP After Last Dose Assessed Using Facial 5-point Hedonic Scale
Palatability of IMP after the last dose in participants aged 2 years to less than 18 years was assessed using 5-point hedonic scales in combination with verbal rating. A question "How does the medication taste" was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range with 5 = really good, 4 = good, 3 = a bit good/a bit bad, 2 = bad, and 1 = really bad. Higher scores represent good palatability. Responses were summarized. Missing values were not imputed.
Palatability data was not collected in participants <2 years old.
Up to 96 hours
Acceptability of IMP After Last Dose Assessed Using Facial 5-point Hedonic Scale
Acceptability of IMP in participants aged 2 years to less than 18 years was assessed using 5-point hedonic scales in combination with verbal rating. A question "Swallowing the medication is..." was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range, with 5 = really easy, 4 = easy, 3 = a bit easy/a bit difficult, 2 = difficult, and 1 = really difficult. Higher scores represent better acceptability.
Responses were summarized. Missing values were not imputed. Acceptability data was not collected in participants <2 years old.
Up to 96 hours
Up to 24 hours
Median Amount of Supplemental Opioid Analgesic Medication Use After First Intake of Investigational Medicinal Product in Children Aged From Birth to Less Than 2 Years
The median amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set subset aged from birth to less than 2 years old was determined from 0 to 12 hours and from 0 to 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Up to 24 hours
Stanford
California
94305
United States
US011
Miami
Florida
33136
United States
US012
Louisville
Kentucky
40202
United States
US001
The Bronx
New York
10461
United States
US018
The Bronx
New York
10467
United States
US006
Durham
North Carolina
27710
United States
US016
Cincinnati
Ohio
45229
United States
US015
Philadelphia
Pennsylvania
19104
United States
US014
Pittsburgh
Pennsylvania
15224
United States
US003
Dallas
Texas
75235
United States
US005
Houston
Texas
77030
United States
US007
Milwaukee
Wisconsin
53226
United States
BG003
Pleven
5800
Bulgaria
BG005
Sofia
1606
Bulgaria
BG002
Stara Zagora
600
Bulgaria
HR003
Split
21000
Croatia
HR001
Zagreb
10000
Croatia
CZ004
Fryštát
73506
Czechia
CZ003
Olomouc
77900
Czechia
CZ001
Praha 4 - Krč
14059
Czechia
FR002
La Tronche
38700
France
FR001
Lille
59037
France
FR004
Limoges
87000
France
DE001
Freiburg im Breisgau
79106
Germany
HU004
Budapest
1094
Hungary
HU003
Debrecen
4032
Hungary
PL011
Bydgoszcz
85-094
Poland
PL010
Gdansk
80-803
Poland
PL005
Lodz
93-338
Poland
PL002
Lublin
20-093
Poland
PL009
Olsztyn
10-561
Poland
PL014
Rzeszów
35-301
Poland
PL007
Torun
87-100
Poland
PL004
Warsaw
04-730
Poland
PL008
Warsaw
04-730
Poland
ES002
Barcelona
8950
Spain
ES005
Madrid
28040
Spain
ES007
Madrid
28046
Spain
ES009
Santiago de Compostela
15706
Spain
ES006
Valladolid
47003
Spain
GB003
Bristol
BS2 8BJ
United Kingdom
GB001
Sheffield
S10 2TH
United Kingdom
FG001
Placebo (From 2 to <18 Years)
This arm includes all participants aged 2 years to less than 18 years who had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA or PCA and who received at least 1 dose of placebo oral solution.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours. 24-hour treatment completers were defined as those who did not discontinue treatment before 24 hours; trial completers completed 24 hours of treatment and attended the follow up visit.
FG002
Tapentadol (From Birth to <2 Years)
This arm includes all participants aged from birth (at least 37 weeks gestational age) to less than 2 years who had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA and who received at least 1 dose of tapentadol oral solution.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours. 24-hour treatment completers were defined as those who did not discontinue treatment before 24 hours; trial completers completed 24 hours of treatment and attended the follow up visit.
FG003
Placebo (From Birth to <2 Years)
This arm includes all participants aged from birth (at least 37 weeks gestational age) to less than 2 years who had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA and who received at least 1 dose of placebo oral solution.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours. 24-hour treatment completers were defined as those who did not discontinue treatment before 24 hours; trial completers completed 24 hours of treatment and attended the follow up visit.
FG000108 subjects
FG00152 subjects
FG00211 subjects
FG0034 subjects
COMPLETED
FG00090 subjects
FG00146 subjects
FG00210 subjects
FG0034 subjects
NOT COMPLETED
FG00018 subjects
FG0016 subjects
FG0021 subjects
FG0030 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0003 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
Physician Decision
FG0004 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
Lack of Efficacy
FG0003 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Adverse Event
FG0004 subjects
FG0012 subjects
FG0020 subjects
FG0030 subjects
Recovery (opioid no longer needed)
FG0002 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
Further reasons
FG0002 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
24-hour Treatment and Trial Completion
Type
Comment
Milestone Data
STARTED
FG00090 subjects
FG00146 subjects
FG00210 subjects
FG0034 subjects
COMPLETED
FG00063 subjects
FG00128 subjects
FG0029 subjects
FG0034 subjects
NOT COMPLETED
FG00027 subjects
FG00118 subjects
FG0021 subjects
FG0030 subjects
Type
Comment
Reasons
Physician Decision
FG00010 subjects
FG0015 subjects
FG0020 subjects
FG003
Baseline characteristics are reported separately for 160 participants aged 2 to less than 18 years (included in the Full Analysis Set for the EU PDCO and the US FDA) and for 15 participants aged from birth to less than 2 years (included in the Full Analysis Set for the US FDA). All participants completed 12 hours of treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Tapentadol (From 2 to <18 Years) - 12-h Treatm. Completion
Participants had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA or PCA.
This arm includes all participants aged 2 years to less than 18 years who received at least 1 dose of tapentadol oral solution.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours.
BG001
Placebo (From 2 to <18 Years) - 12-h Treatm. Completion
Participants had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA or PCA.
This arm includes all participants aged 2 years to less than 18 years who received at least 1 dose of placebo.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours.
BG002
Tapentadol (From Birth to <2 Years) - 12-h Treatm. Completion
Participants had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA.
This arm includes all participants aged from birth (at least 37 weeks gestational age) to less than 2 years who received at least 1 dose of tapentadol oral solution.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours.
BG003
Placebo (From Birth to <2 Years) - 12-h Treatm. Completion
Participants had undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment via NCA.
This arm includes all participants aged from birth (at least 37 weeks gestational age) to less than 2 years who received at least 1 dose of placebo.
12-hour treatment period completers were defined as participants who did not discontinue the treatment period before 12 hours.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000108
BG00152
BG00211
BG0034
BG004175
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Full Range
years
Title
Denominators
Categories
Title
Measurements
BG00010.8(2 to 17)
BG00110.4(2 to 17)
BG0020.74(0.1 to 1.6)
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Children (2 to <12 years)
Title
Measurements
BG00055
BG00127
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00053
BG00123
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00021
BG0019
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Hungary
Title
Measurements
BG0004
BG0013
BG002
Height
Mean
Full Range
centimeter
Title
Denominators
Categories
Title
Measurements
BG000145(87 to 185)
BG001143.3(72 to 193)
BG002
Weight
Mean
Full Range
kg
Title
Denominators
Categories
Title
Measurements
BG00043.09(11.0 to 98.2)
BG00142.22(10.7 to 89.1)
BG002
Body Mass Index
Mean
Full Range
kg per square meter
Title
Denominators
Categories
Title
Measurements
BG00018.83(9.5 to 29.7)
BG00119.12(13.9 to 31.4)
BG002
Amount of morphine or hydromorphone taken prior to IMP
Mean
Full Range
mg/kg
Title
Denominators
Categories
Title
Measurements
BG0000.59(0.0 to 8.8)
BG0010.45(0.0 to 3.7)
BG002
Type of opioid analgesia used
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hydromorphone
BG00033
BG00118
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
For the US FDA: The Total Amount of Supplemental Opioid Analgesic Medication Used Within the First 12 Hours After First Intake of Investigational Medicinal Product (IMP) [Tapentadol Oral Solution or Placebo]
The primary endpoint for the United States Food and Drug Administration (US FDA) (and secondary endpoint for the Pediatric Committee of the European Medicines Agency [EU PDCO]) was the total amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set (from 2 years to <18 years old) within 12 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Full Analysis Set; subset of 160 participants from 2 to less than 18 years included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Least Squares Mean
Standard Error
mg/kg
Up to 12 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG000108
OG00152
Title
Denominators
Categories
Title
Measurements
OG0000.08± 0.01
OG0010.13± 0.02
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
The endpoint was analyzed using an analysis of variance model. This included treatment, baseline age group, and the used SOAM as factors. For participants discontinuing treatment before 12 hours for any other reason than no further need of opioid analgesics or switch to exclusively oral opioid analgesics, cumulative SOAM use over the respective time period was based on the observed SOAM use up to the time of the participant's discontinuation.
ANOVA
0.0404
Mean Difference (Final Values)
-0.05
Standard Error of the Mean
0.02
2-Sided
95
-0.09
0
Superiority
Primary
For the EU PDCO: The Total Amount of Supplemental Opioid Analgesic Medication Used Within the First 24 Hours After First Intake of IMP [Tapentadol Oral Solution or Placebo]
The primary endpoint for the EU PDCO (and secondary endpoint for the US FDA) was the total amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set (from 2 years to <18 years old) within 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Full Analysis Set; subset of 160 participants from 2 to less than 18 years included in the analysis; if by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Least Squares Mean
Standard Error
mg/kg
Up to 24 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Total Amount of Supplemental Opioid Analgesic Medication Received, Assessed in 12-hour Intervals From 24 Hours to 96 Hours After the First Dose of IMP
The total amount of supplemental opioid analgesic medication (SOAM) received was assessed in 12-hour intervals from 24 hours to 96 hours after the first dose of IMP for participants who were administered SOAM.
SOAM use was expressed in mg/kg of morphine i.v. equivalents.
Full Analysis Set; 175 participants aged from birth to <18 years; participants with no documented SOAM use in the respective time period are excluded from calculations. When 0 participants are indicated in the Row Analyzed that means no data was collected.
Posted
Mean
Full Range
mg/kg
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
OG002
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
Secondary
Palatability of IMP After First Dose Assessed Using Facial 5-point Hedonic Scale
Palatability of IMP after the first dose was assessed in participants aged 2 years to less than 18 years using 5-point hedonic scales in combination with verbal rating. A question "How does the medication taste" was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range where 5 = really good, 4 = good, 3 = a bit good/a bit bad, 2 = bad, and 1 = really bad. Higher scores represent good palatability. Responses were summarized. Missing values were not imputed.
Palatability data was not collected for participants <2 years old.
Full Analysis Set; subset of 160 participants aged from 2 years to less than 18 years included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Count of Participants
Participants
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Acceptability of IMP After First Dose Assessed Using Facial 5-point Hedonic Scale
Acceptability of IMP in participants aged 2 years to less than 18 years was assessed using 5-point hedonic scales in combination with verbal rating. A question "Swallowing the medication is..." was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range, with 5 = really easy, 4 = easy, 3 = a bit easy/a bit difficult, 2 = difficult, and 1 = really difficult. Higher scores represent better acceptability.
Responses were summarized. Missing values were not imputed. Acceptability data was not collected in participants <2 years old.
Full Analysis Set: subset of 160 participants aged from 2 years to <18 years included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Count of Participants
Participants
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Change From Baseline in the Face, Leg, Activity, Cry, and Consolability (FLACC) Total Score in Participants Aged Less Than 6 Years
The FLACC scale was used for children from birth to less than 6 years, or in older children who were not able to report their pain using the other scales. This tool includes 5 categories of pain behaviors: facial expression (F), leg movement (L), activity (A), cry (C), and consolability (C). Each of the 5 categories is scored 0, 1 or 2. The total score between 0 and 10 is the sum of the 5 individual categories. Higher scores represent worse condition.
The Pain intensity scores were obtained before and after first dose of IMP, and before each subsequent dose of IMP, whenever possible, up to end of treatment (96 hours).
Changes from baseline values were summarized descriptively for each time point.
Full Analysis Set: subset of 51 participants aged from birth to <6 years included in the analysis; participants with missing data were excluded from calculations. No standard deviations were derived for less than 5 participants.
Posted
Mean
Full Range
score on a scale
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <6 Years)
This analysis subset included all participants aged 2 years to less than 6 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <6 Years)
This analysis subset included all participants aged 2 years to less than 6 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Change From Baseline Pain Intensity Using the Faces Pain Scale-Revised (FPS-R) in Participants Aged 6 to Less Than 12 Years
For children aged 6 years (if possible) to less than 12 years, pain intensity was assessed by the use of the Faces Pain Scale-Revised (FPS-R). The FPS-R is a validated self-reported 6-point scale (0, 2, 4, 6, 8, 10) with 0 representing no pain and 10 representing very much pain. Facial representations were used to indicate how much the pain hurts. Higher scores represent worse condition.
Pain intensity scores were obtained before and after first dose of IMP, and before each subsequent dose of IMP, whenever possible.
Changes from baseline pain values were summarized descriptively for each time point up to end of treatment (96 hours).
Full Analysis Set: subset of 46 participants aged from 6 to less than 12 years included in the analysis; participants with missing data are not included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Mean
Standard Deviation
units on a scale
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (6 to <12 Years)
This analysis subset included all participants aged 6 years to less than 12 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (6 to <12 Years)
This analysis subset included all participants aged 6 years to less than 12 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Change From Baseline in the Visual Analog Scale (VAS) Pain Intensity Score in Participants Aged 12 to Less Than 18 Years
For children and adolescents aged 12 years to less than 18 years, pain intensity was assessed by the use of a Visual analog scale (VAS). The participant was asked to draw a single line to indicate the current level of pain intensity on a 100 mm long scale by marking a point on the line in response to: "My pain right now is". The mark was scored between "no pain" and "pain as bad as it could be". A value of 0 indicates "no pain". A value of 100 indicates "pain as bad as it could be". Pain intensity scores were obtained before and after first dose of IMP, and before each subsequent dose of IMP, whenever possible. Changes from baseline values were summarized descriptively for each time point.
Full Analysis Set: subset of 78 participants aged from 12 to less than 18 years included in the analysis; participants with missing data are not included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Mean
Standard Deviation
units on a scale
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (12 to <18 Years)
This analysis subset included all participants aged 12 years to less than 18 years old who were allocated to Tapentadol and received at least one dose of IMP.
OG001
Placebo (12 to <18 Years)
Secondary
Clinical Global Impression of Change (CGIC)
The CGIC was assessed at the End of Treatment Visit (Day 4). The investigator rated the participant's global improvement and satisfaction with the treatment on a 7-point scale with 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worsening. Results were summarized descriptively.
Full Analysis Set; 175 participants from birth to less than 18 years are included. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Count of Participants
Participants
Day 4
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
OG002
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
Secondary
Patient Global Impression of Change (PGIC)
The PGIC was assessed at the End of Treatment Visit (Day 4). Participants rated their impression of overall status on a 7-point scale with 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Higher scores indicate worsening. If participants were not capable of completing the questionnaire, the parent/legal guardian could completed the questionnaire on behalf of the participant.
Results were summarized descriptively.
Full Analysis Set; 175 participants from birth to less than 18 years are included. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Count of Participants
Participants
Day 4
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
OG002
Tapentadol (From Birth to <2 Years)
Secondary
Time to Receive First and Second Patient- or Nurse-controlled Analgesia After the First Dose of IMP
The time to first and time to second patient-controlled analgesia (PCA) or nurse-controlled analgesia (NCA) after the first dose of IMP were summarized descriptively using time-to-event methods and are displayed by relevant treatment groups. Participants who completed the End of Treatment Visit (scheduled for 96 hours after first IMP) before their first/second use of NCA/PCA or participants who terminated treatment before their first/second use of NCA/PCA were censored at the End of Treatment Visit.
Time-to-event variables are reported using Kaplan-Meier analyses. Therefore, values might remain missing if the survival function does not reach a respective threshold. This is indicated by not applicable (NA).
Full Analysis Set; 175 participants from birth to less than 18 years are included, censored participants are not displayed. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Median
95% Confidence Interval
minutes
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Time From First Dose of IMP Until Treatment Discontinuation Due to Lack of Efficacy
The distributions of the time from the first dose of IMP to treatment discontinuation due to lack of efficacy were summarized descriptively using time-to-event methods.
Participants who reached the maximum duration of treatment (72 hours) were censored at 72 hours after first IMP intake. Participants who discontinued during the Treatment Period for reasons other than lack of efficacy were censored at the time of the decision to discontinue treatment.
Due to the low number of participants with events in the age group from 2 to <18 years, the median time and the corresponding confidence interval could not be calculated. The number of participants who discontinued early due to lack of efficacy is presented instead.
Full Analysis Set; 160 participants from 2 to less than 18 years were included in the analysis. If by error a participant did not receive the allocated medication, he/she was evaluated as allocated following the intention-to-treat principle. No participant <2 years was discontinued from treatment due to lack of efficacy; no analysis was performed.
Posted
Count of Participants
Participants
Up to 72 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
Secondary
Palatability of IMP After Last Dose Assessed Using Facial 5-point Hedonic Scale
Palatability of IMP after the last dose in participants aged 2 years to less than 18 years was assessed using 5-point hedonic scales in combination with verbal rating. A question "How does the medication taste" was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range with 5 = really good, 4 = good, 3 = a bit good/a bit bad, 2 = bad, and 1 = really bad. Higher scores represent good palatability. Responses were summarized. Missing values were not imputed.
Palatability data was not collected in participants <2 years old.
Full Analysis Set; participants aged 2 to less than 18 years were included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Count of Participants
Participants
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Secondary
Acceptability of IMP After Last Dose Assessed Using Facial 5-point Hedonic Scale
Acceptability of IMP in participants aged 2 years to less than 18 years was assessed using 5-point hedonic scales in combination with verbal rating. A question "Swallowing the medication is..." was asked and the verbal rating was from really good, good, a bit good/a bit bad, bad, and really bad. The pictorial scale of facial expressions was co-related with verbal rating range, with 5 = really easy, 4 = easy, 3 = a bit easy/a bit difficult, 2 = difficult, and 1 = really difficult. Higher scores represent better acceptability.
Responses were summarized. Missing values were not imputed. Acceptability data was not collected in participants <2 years old.
Full Analysis Set; 160 participants aged 2 to less than 18 years were included in the analysis. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Count of Participants
Participants
Up to 96 hours
ID
Title
Description
OG000
Tapentadol (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From 2 to <18 Years)
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Other Pre-specified
Mean Amount of Supplemental Opioid Analgesic Medication Use After First Intake of Investigational Medicinal Product in Children Aged From Birth to Less Than 2 Years
The mean amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set subset aged from birth to less than 2 years old was determined from 0 to 12 hours and from 0 to 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Full Analysis Set: subset of 15 participants from birth to less than 2 years included in the analysis; participants with missing data were excluded from calculations. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Mean
Full Range
mg/kg
Up to 24 hours
ID
Title
Description
OG000
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Other Pre-specified
Median Amount of Supplemental Opioid Analgesic Medication Use After First Intake of Investigational Medicinal Product in Children Aged From Birth to Less Than 2 Years
The median amount of supplemental opioid analgesic medication (SOAM) used in the Full Analysis Set subset aged from birth to less than 2 years old was determined from 0 to 12 hours and from 0 to 24 hours after first intake of IMP. SOAM use is expressed in mg/kg of morphine i.v. equivalents.
Full Analysis Set: subset of 15 participants from birth to less than 2 years included in the analysis; participants with missing data were excluded from calculations. If by error a participant did not receive the allocated medication, the participant was evaluated as allocated following the intention-to-treat principle.
Posted
Median
Full Range
mg/kg
Up to 24 hours
ID
Title
Description
OG000
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
OG001
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Time Frame
Any adverse event (AE) is reported that started at or after the first dose of IMP or started before the first dose of IMP and worsened in intensity after the first dose of IMP up to the end of the therapeutic reach of the last dose of IMP. The therapeutic reach is the time after IMP intake that a participant is still considered to be potentially affected by the study drug. For tapentadol oral solution, the therapeutic reach is defined as 48 hours.
Description
Adverse events are reported for all participants who received at least 1 dose of IMP (tapentadol or placebo) (Safety Set).
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Overall (From 2 to <18 Years)
All participants aged 2 years to below 18 years who received at least 1 dose of IMP.
0
160
2
160
87
160
EG001
Tapentadol (From 2 to <18 Years)
All participants aged 2 years to below 18 years who received at least 1 dose of tapentadol oral solution.
0
108
2
108
61
108
EG002
Placebo (From 2 to <18 Years)
All participants aged 2 years to below 18 years who received at least 1 dose of placebo oral solution.
0
52
0
52
26
52
EG003
Overall (From Birth to <2 Years)
All participants from birth to below 2 years who received at least 1 dose of IMP.
0
15
0
15
9
15
EG004
Tapentadol (From Birth to <2 Years)
All participants from birth to below 2 years who received at least 1 dose of tapentadol oral solution.
0
11
0
11
6
11
EG005
Placebo (From Birth to <2 Years)
All participants from birth to below 2 years who received at least 1 dose of placebo oral solution.
0
4
0
4
3
4
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal abscess
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG0030 events0 affected15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
Seizure
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Chest pain
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG0030 events0 affected15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
Face oedema
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Infusion site pruritus
General disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Pyrexia
General disorders
MedDRA 19.1
Systematic Assessment
EG00020 events11 affected160 at risk
EG00119 events10 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Agitation
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Hallucinations, mixed
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Initial insomnia
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0002 events2 affected160 at risk
EG0010 events0 affected108 at risk
EG0022 events2 affected52 at risk
EG003
Withdrawal syndrome
Psychiatric disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Anaemia postoperative
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0002 events2 affected160 at risk
EG0011 events1 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Transfusion reaction
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Administration related reaction
Injury, poisoning and procedural complications
MedDRA 19.1
Systematic Assessment
EG0000 events0 affected160 at risk
EG0010 events0 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Blood urea decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Haematocrit decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Oxygen saturation decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0005 events4 affected160 at risk
EG0014 events3 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Po2 decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0002 events1 affected160 at risk
EG0012 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Red blood cell count decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Respiratory rate decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0000 events0 affected160 at risk
EG0010 events0 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Haemoglobin decreased
Investigations
MedDRA 19.1
Systematic Assessment
EG0002 events2 affected160 at risk
EG0011 events1 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Anaemia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Haemorrhagic anaemia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Thrombocytopenia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Sinus Tachycardia
Cardiac disorders
MedDRA 19.1
Systematic Assessment
EG0003 events3 affected160 at risk
EG0012 events2 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Bradypnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Chylothorax
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0003 events3 affected160 at risk
EG0013 events3 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Nasal Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Painful Respiration
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0010 events0 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Pleural Effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0008 events5 affected160 at risk
EG0017 events4 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Headache
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0007 events6 affected160 at risk
EG0016 events5 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Sedation
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0002 events2 affected160 at risk
EG0012 events2 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 19.1
Systematic Assessment
EG0008 events8 affected160 at risk
EG0016 events6 affected108 at risk
EG0022 events2 affected52 at risk
EG003
Eye pain
Eye disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Abdominal Pain
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG00017 events17 affected160 at risk
EG00111 events11 affected108 at risk
EG0026 events6 affected52 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG00027 events20 affected160 at risk
EG00122 events16 affected108 at risk
EG0025 events4 affected52 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG00044 events31 affected160 at risk
EG00136 events25 affected108 at risk
EG0028 events6 affected52 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 events0 affected160 at risk
EG0010 events0 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 events0 affected160 at risk
EG0010 events0 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Impaired gastric emptying
Gastrointestinal disorders
MedDRA 19.1
Systematic Assessment
EG0000 events0 affected160 at risk
EG0010 events0 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 19.1
Systematic Assessment
EG0004 events4 affected160 at risk
EG0013 events3 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0007 events7 affected160 at risk
EG0014 events4 affected108 at risk
EG0023 events3 affected52 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0003 events1 affected160 at risk
EG0013 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Decreased Appetite
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0002 events2 affected160 at risk
EG0011 events1 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0002 events2 affected160 at risk
EG0011 events1 affected108 at risk
EG0021 events1 affected52 at risk
EG003
Lactic Acidosis
Metabolism and nutrition disorders
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
Pneumonia mycoplasmal
Infections and infestations
MedDRA 19.1
Systematic Assessment
EG0001 events1 affected160 at risk
EG0011 events1 affected108 at risk
EG0020 events0 affected52 at risk
EG003
See primary endpoint for the US FDA.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The sponsor reserves the right to review any proposed presentation of the results of this trial before they are submitted for publication or public disclosure. Neither party (e.g., the sponsor, the coordinating investigator) has the right to prohibit publication or public disclosure unless it can be shown to affect possible patent rights.
The endpoint was analyzed using an analysis of variance model. This included treatment, baseline age group, and the used supplemental opioid analgesic medication (SOAM) as factors. For participants discontinuing treatment before 24 hours for any other reason than no further need of SOAM or switch to exclusively oral opioid analgesics, cumulative SOAM use over the respective time period was based on the observed SOAM use up to the time of the participant's discontinuation.
ANOVA
0.0154
Mean Difference (Final Values)
-0.1
Standard Error of the Mean
0.04
2-Sided
95
-0.18
-0.02
Superiority
OG003
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG000108
OG00152
OG00211
OG0034
Title
Denominators
Categories
24 h to 36 h
ParticipantsOG00038
ParticipantsOG00119
ParticipantsOG0021
ParticipantsOG0031
Title
Measurements
OG0000.08(0.0 to 0.4)
OG0010.14(0.0 to 0.7)
OG0020.020(0.02 to 0.02)
OG003
36 h to 48 h
ParticipantsOG00030
ParticipantsOG00112
ParticipantsOG0021
ParticipantsOG0031
48 h to 60 h
ParticipantsOG00020
ParticipantsOG0018
ParticipantsOG0020
ParticipantsOG0030
60 h to 72 h
ParticipantsOG00010
ParticipantsOG0016
ParticipantsOG0020
ParticipantsOG0030
72 h to 84 h
ParticipantsOG0003
ParticipantsOG0012
ParticipantsOG0020
ParticipantsOG0030
84 h to 96 h
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
ParticipantsOG0030
Units
Counts
Participants
OG000108
OG00152
Title
Denominators
Categories
Really bad
Title
Measurements
OG00013
OG0012
Bad
Title
Measurements
OG00028
OG0012
A bit bad / a bit good
Title
Measurements
OG00036
OG00110
Good
Title
Measurements
OG00024
OG00124
Really good
Title
Measurements
OG0006
OG00111
Missing
Title
Measurements
OG0001
OG0013
Units
Counts
Participants
OG000108
OG00152
Title
Denominators
Categories
Title
Measurements
Really difficult
OG0001
OG0010
Difficult
OG0007
OG0013
A bit difficult/a bit easy
OG00017
OG0017
Easy
OG00046
OG00120
Really easy
OG00035
OG00119
Missing
OG0002
OG0013
OG002
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
OG003
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG00023
OG00113
OG00211
OG0034
Title
Denominators
Categories
30-60 mins after 1st IMP
ParticipantsOG00022
ParticipantsOG00113
ParticipantsOG00211
ParticipantsOG0034
Title
Measurements
OG0001.1(-5.0 to 4.0)
OG0011.9(0.0 to 6.0)
OG0021.4(-4.0 to 6.0)
OG003
Before 2nd dose of IMP
ParticipantsOG00023
ParticipantsOG00113
ParticipantsOG00211
ParticipantsOG0034
Before 3rd dose of IMP
ParticipantsOG00023
ParticipantsOG00113
ParticipantsOG00210
ParticipantsOG0034
Before 4th dose of IMP
ParticipantsOG00021
ParticipantsOG00112
ParticipantsOG00210
ParticipantsOG0034
Before 5th dose of IMP
ParticipantsOG00020
ParticipantsOG00111
ParticipantsOG00210
ParticipantsOG0034
Before 6th dose of IMP
ParticipantsOG00019
ParticipantsOG0018
ParticipantsOG00210
ParticipantsOG0034
Before 7th dose of IMP
ParticipantsOG00019
ParticipantsOG0018
ParticipantsOG0028
ParticipantsOG0033
Before 8th dose of IMP
ParticipantsOG00013
ParticipantsOG0015
ParticipantsOG0025
ParticipantsOG0032
At End of Treatment
ParticipantsOG00023
ParticipantsOG00113
ParticipantsOG00211
ParticipantsOG0034
Units
Counts
Participants
OG00032
OG00114
Title
Denominators
Categories
30-60 mins after 1st IMP
ParticipantsOG00030
ParticipantsOG00114
Title
Measurements
OG0001.0± 1.72
OG0010.7± 1.86
Before 2nd dose of IMP
ParticipantsOG00027
ParticipantsOG00112
Title
Measurements
OG0001.0± 2.5
OG001
Before 3rd dose of IMP
ParticipantsOG00026
ParticipantsOG00112
Title
Measurements
OG0001.0± 2.35
OG001
Before 4th dose of IMP
ParticipantsOG00024
ParticipantsOG00112
Title
Measurements
OG0001.3± 2.33
OG001
Before 5th dose of IMP
ParticipantsOG00024
ParticipantsOG00111
Title
Measurements
OG0000.8± 2.75
OG001
Before 6th dose of IMP
ParticipantsOG00023
ParticipantsOG00110
Title
Measurements
OG0000.5± 2.43
OG001
Before 7th dose of IMP
ParticipantsOG00021
ParticipantsOG0019
Title
Measurements
OG0002.0± 2.37
OG001
Before 8th dose of IMP
ParticipantsOG00014
ParticipantsOG0019
Title
Measurements
OG0001.3± 2.55
OG001
At End of Treatment
ParticipantsOG00032
ParticipantsOG00114
Title
Measurements
OG0002.8± 2.93
OG001
This analysis subset included all participants aged 12 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG00053
OG00125
Title
Denominators
Categories
30-60 mins after 1st IMP
ParticipantsOG00050
ParticipantsOG00125
Title
Measurements
OG0008.0± 18.67
OG0016.4± 19.58
Before 2nd dose of IMP
ParticipantsOG00048
ParticipantsOG00124
Title
Measurements
OG0006.5± 23.61
OG001
Before 3rd dose of IMP
ParticipantsOG00044
ParticipantsOG00122
Title
Measurements
OG00013.1± 25.09
OG001
Before 4th dose of IMP
ParticipantsOG00044
ParticipantsOG00122
Title
Measurements
OG0008.8± 29.01
OG001
Before 5th dose of IMP
ParticipantsOG00042
ParticipantsOG00120
Title
Measurements
OG00013.0± 22.92
OG001
Before 6th dose of IMP
ParticipantsOG00038
ParticipantsOG00117
Title
Measurements
OG00013.0± 24.74
OG001
Before 7th dose of IMP
ParticipantsOG00028
ParticipantsOG00113
Title
Measurements
OG00010.7± 25.77
OG001
Before 8th dose of IMP
ParticipantsOG00019
ParticipantsOG0017
Title
Measurements
OG00012.2± 28.91
OG001
At End of Treatment
ParticipantsOG00051
ParticipantsOG00125
Title
Measurements
OG00011.0± 27.87
OG001
OG003
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG000108
OG00152
OG00211
OG0034
Title
Denominators
Categories
Title
Measurements
Very much improved
OG00015
OG00112
OG0023
OG0031
Much improved
OG00058
OG00122
OG0022
OG0032
Minimally improved
OG00018
OG0018
OG0021
OG0031
No change
OG00011
OG0014
OG0022
OG0030
Minimally worse
OG0003
OG0012
OG0021
OG0030
Much worse
OG0001
OG0011
OG0020
OG0030
Very much worse
OG0000
OG0010
OG0020
OG0030
Missing
OG0002
OG0013
OG0022
OG0030
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
OG003
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG000108
OG00152
OG00211
OG0034
Title
Denominators
Categories
Title
Measurements
Very much improved
OG00016
OG00111
OG0024
OG0033
Much improved
OG00053
OG00123
OG0021
OG0031
Minimally improved
OG00021
OG00112
OG0021
OG0030
No change
OG00013
OG0013
OG0022
OG0030
Minimally worse
OG0001
OG0010
OG0020
OG0030
Much worse
OG0001
OG0010
OG0020
OG0030
Very much worse
OG0000
OG0010
OG0020
OG0030
Missing
OG0003
OG0013
OG0023
OG0030
OG002
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
OG003
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG000108
OG00152
OG00211
OG0034
Title
Denominators
Categories
Time to first NCA/PCA administration
ParticipantsOG00081
ParticipantsOG00146
ParticipantsOG0026
ParticipantsOG0033
Title
Measurements
OG000183.0(90.0 to 446.0)
OG001131.5(74.0 to 216.0)
OG002960.0(80.0 to NA)Survival function did not reach threshold.
OG003
Time to second NCA/PCA administration
ParticipantsOG00066
ParticipantsOG00137
ParticipantsOG0024
ParticipantsOG0031
This analysis subset included all participants aged 2 years to less than 18 years old who were allocated to placebo and received at least one dose of IMP.
OG002
Tapentadol (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to tapentadol and received at least one dose of IMP.
OG003
Placebo (From Birth to <2 Years)
This analysis subset included all participants aged from birth to less than 2 years old who were allocated to placebo and received at least one dose of IMP.
Units
Counts
Participants
OG000108
OG00152
OG00211
OG0034
Title
Denominators
Categories
Title
Measurements
Number of censored participants
OG000104
OG00148
OG00211
OG0034
Number of participants with event
OG0004
OG0014
OG0020
OG0030
Units
Counts
Participants
OG000108
OG00152
Title
Denominators
Categories
Really bad
Title
Measurements
OG00014
OG0011
Bad
Title
Measurements
OG00015
OG0013
A bit bad / a bit good
Title
Measurements
OG00038
OG00114
Good
Title
Measurements
OG00028
OG00116
Really good
Title
Measurements
OG0005
OG00112
Missing
Title
Measurements
OG0008
OG0016
Units
Counts
Participants
OG000108
OG00152
Title
Denominators
Categories
Title
Measurements
Really difficult
OG0003
OG0010
Difficult
OG0006
OG0012
A bit difficult/a bit easy
OG0009
OG0016
Easy
OG00043
OG00118
Really easy
OG00039
OG00120
Missing
OG0008
OG0016
Units
Counts
Participants
OG00011
OG0014
Title
Denominators
Categories
0-12 hours
Title
Measurements
OG0000.03(0 to 0.07)
OG0010.01(0 to 0.04)
0-24 hours
Title
Measurements
OG0000.054(0 to 0.3)
OG0010.016(0 to 0.04)
Units
Counts
Participants
OG00011
OG0014
Title
Denominators
Categories
0-12 hours
Title
Measurements
OG0000.00(0 to 0.07)
OG0010.01(0 to 0.04)
0-24 hours
Title
Measurements
OG0000.016(0 to 0.3)
OG0010.013(0 to 0.04)
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0040 events0 affected11 at risk
EG0051 events1 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0040 events0 affected11 at risk
EG0051 events1 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
2 events
2 affected
15 at risk
EG0042 events2 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0041 events1 affected11 at risk
EG0050 events0 affected4 at risk
1 events
1 affected
15 at risk
EG0040 events0 affected11 at risk
EG0051 events1 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0 events
0 affected
15 at risk
EG0040 events0 affected11 at risk
EG0050 events0 affected4 at risk
0.003
(0.003 to 0.003)
Title
Measurements
OG0000.06(0.0 to 0.4)
OG0010.06(0.0 to 0.4)
OG0020.000(0.00 to 0.00)
OG0030.000(0.00 to 0.00)
Title
Measurements
OG0000.05(0.0 to 0.4)
OG0010.06(0.0 to 0.4)
Title
Measurements
OG0000.06(0.0 to 0.2)
OG0010.03(0.0 to 0.2)
Title
Measurements
OG0000.0(0.0 to 0.0)
OG0010.0(0.0 to 0.0)
2.8
(0.0 to 5.0)
Title
Measurements
OG0001.4(-2.0 to 7.0)
OG0011.3(0.0 to 6.0)
OG0020.7(-5.0 to 6.0)
OG0031.0(0.0 to 2.0)
Title
Measurements
OG0001.7(-2.0 to 7.0)
OG0011.6(-1.0 to 6.0)
OG0022.0(0.0 to 6.0)
OG003-1.3(-6.0 to 2.0)
Title
Measurements
OG0001.4(-2.0 to 5.0)
OG0011.3(-1.0 to 6.0)
OG0021.3(-5.0 to 5.0)
OG0030.0(-5.0 to 3.0)
Title
Measurements
OG0001.8(-1.0 to 5.0)
OG0011.9(-1.0 to 6.0)
OG0021.4(-2.0 to 6.0)
OG0032.0(0.0 to 4.0)
Title
Measurements
OG0001.6(-2.0 to 5.0)
OG0012.3(0 to 6.0)
OG0022.0(-1.0 to 6.0)
OG0032.5(0.0 to 5.0)
Title
Measurements
OG0001.6(-2.0 to 6.0)
OG0012.1(0.0 to 6.0)
OG0021.9(-1.0 to 6.0)
OG0032.0(0.0 to 3.0)
Title
Measurements
OG0001.2(-1.0 to 4.0)
OG0012.2(-3.0 to 6.0)
OG0023.8(1.0 to 6.0)
OG003-0.5(-5.0 to 4.0)
Title
Measurements
OG0002.4(-3.0 to 6.0)
OG0012.0(-1.0 to 9.0)
OG0022.1(-4.0 to 6.0)
OG0033.5(0.0 to 7.0)
0.5
± 2.84
-0.2
± 2.17
-0.3
± 3.7
0
± 2.19
0.2
± 2.2
0.7
± 2.24
0.2
± 2.73
3.4
± 3.56
6.0
± 19.36
5.9
± 22.11
5.1
± 21.7
-2.7
± 34.4
6.6
± 28.4
15.0
± 20.27
11.9
± 14.6
11.4
± 28.47
155.0
(124.0 to NA)
Survival function did not reach threshold.
Title
Measurements
OG000572.0(321.0 to 1993.0)
OG001388.0(194.0 to 820.0)
OG002NA(210 to NA)Survival function did not reach threshold.
OG003NA(500.0 to NA)Survival function did not reach threshold.